The effect of cleft lip on adults' responses to faces: cross-species findings

Cleft lip and palate is the most common of the congenital conditions affecting the face and cranial bones and is associated with a raised risk of difficulties in infant-caregiver interaction; the reasons for such difficulties are not fully understood. Here, we report two experiments designed to explore how adults respond to infant faces with and without cleft lip, using behavioural measures of attractiveness appraisal ('liking') and willingness to work to view or remove the images ('wanting'). We found that infants with cleft lip were rated as less attractive and were viewed for shorter durations than healthy infants, an effect that was particularly apparent where the cleft lip was severe. Women rated the infant faces as more attractive than men did, but there were no differences in men and women's viewing times of these faces. In a second experiment, we found that the presence of a cleft lip in domestic animals affected adults' 'liking' and 'wanting' responses in a comparable way to that seen for human infants. Adults' responses were also remarkably similar for images of infants and animals with cleft lip, although no gender difference in attractiveness ratings or viewing times emerged for animals. We suggest that the presence of a cleft lip can substantially change the way in which adults respond to human and animal faces. Furthermore, women may respond in different ways to men when asked to appraise infant attractiveness, despite the fact that men and women 'want' to view images of infants for similar durations.     

Integrated models of livestock systems for climate change studies. 2. Intensive systems

The potential impact of climate change by the year 2050 on intensive livestock systems in Britain is assessed through the use of simulation models of farming systems. The submodels comprise livestock feeding, livestock thermal balance and the thermal balance of controlled environment buildings and a stochastic weather generator. These are integrated to form system models for growing pigs and broiler chickens. They are applied to scenarios typical of SE England, which is the warmest region of the country and represents the worst case. For both species the frequency of severe heat stress is substantially increased, with a consequent risk of mortality. To offset this, it would be necessary to reduce stocking densities considerably, or to invest in improved ventilation or cooling equipment. Other effects on production are likely to be small.     

Spatially distinct binding of Cdc42 to PAK1 and N-WASP in breast carcinoma cells

While a significant amount is known about the biochemical signaling pathways of the Rho family GTPase Cdc42, a better understanding of how these signaling networks are coordinated in cells is required. In particular, the predominant subcellular sites where GTP-bound Cdc42 binds to its effectors, such as p21-activated kinase 1 (PAK1) and N-WASP, a homolog of the Wiskott-Aldritch syndrome protein, are still undetermined. Recent fluorescence resonance energy transfer (FRET) imaging experiments using activity biosensors show inconsistencies between the site of local activity of PAK1 or N-WASP and the formation of specific membrane protrusion structures in the cell periphery. The data presented here demonstrate the localization of interactions by using multiphoton time-domain fluorescence lifetime imaging microscopy (FLIM). Our data here establish that activated Cdc42 interacts with PAK1 in a nucleotide-dependent manner in the cell periphery, leading to Thr-423 phosphorylation of PAK1, particularly along the lengths of cell protrusion structures. In contrast, the majority of GFP-N-WASP undergoing FRET with Cy3-Cdc42 is localized within a transferrin receptor- and Rab11-positive endosomal compartment in breast carcinoma cells. These data reveal for the first time distinct spatial association patterns between Cdc42 and its key effector proteins controlling cytoskeletal remodeling.     

Additivity in murine circadian phototransduction

Additivity in the circadian phototransduction system of the mouse has not been tested directly. Because of this, accurate prediction of circadian phase shifts elicited by polychromatic light stimuli cannot be derived from the results of studies using monochromatic light stimuli. This limitation also makes it impossible to deduce the relative contributions of the photoreceptive mechanisms (rods, cones and melanopsin-containing retinal ganglion cells) underlying circadian phototransduction in the mouse. Using nearly monochromatic light stimuli of different spectral composition, and combinations thereof, we demonstrated that murine circadian phototransduction exhibits additivity. Based on the locomotor activity phase shifts elicited by these stimuli, we developed the first quantitative assessment of the relative contributions of conventional and novel photoreceptive mechanisms for circadian functioning in the mouse.     

New transport assay demonstrates vesicular acetylcholine transporter has many alternative substrates

The acetylcholine-binding site in vesicular acetylcholine transporter faces predominantly toward the outside of the vesicle when resting but predominantly toward the inside when transporting. Transport-related reorientation is detected by an ATP-induced decrease in the ability of saturating substrate to displace allosterically bound [(3)H]vesamicol. The assay was used here to determine whether structurally diverse compounds are transported by rat VAChT expressed in PC12(A123.7) cells. Competition by ethidium, tetraphenylphosphonium and other monovalent organic cations with [(3)H]vesamicol is decreased when ATP is added, and the effect depends on proton-motive force. The results indicate that many organic molecules carrying +1 charge are transported, even though the compounds do not resemble acetylcholine in structural details.     

Nitrogen outputs from fecal and urine deposition of small mammals: implications for nitrogen cycling

The contribution of small mammals to nitrogen cycling could have repercussions for the producer community in the maintaining or perhaps magnifying of nitrogen availability. Our objective was to model nitrogen outputs (deposition of feces and urine) of small mammals in an old-field ecosystem and estimate the amount of fecal and urinary nitrogen deposited annually. To address this objective, we used models from laboratory studies and combined these with data from field studies to estimate dietary nitrogen and monthly and annual nitrogen outputs from fecal and urine deposition of five rodent species. The models accounted for monthly fluctuations in density and biomass of small-mammal populations. We estimated that the minimal amount of nitrogen deposited by rodents was 1.0 (0.9–1.1) and 2.7 (2.6–2.9) kg Nha⁻¹ year⁻¹ from feces and urine, respectively, for a total contribution of 3.7 (3.5–4.0) kg Nha⁻¹ year⁻¹. Hispid cotton rats (Sigmodon hispidus) accounted for >75% of the total nitrogen output by small mammals. Our estimates of annual fecal and urinary nitrogen deposited by rodents were comparable to nitrogen deposits by larger herbivores and other nitrogen fluxes in grassland ecosystems and should be considered when assessing the potential effects of herbivory on terrestrial nitrogen cycles.     

Testing alternative explanations of character shifts against ecological character displacement in brook sticklebacks (<Emphasis Type="Italic">Culaea inconstans</Emphasis>) that coexist with ninespine sticklebacks (<Emphasis Type="Italic">Pungitius pungitius</Emphasis>)

Ecological character displacement (ECD) provides opportunities to test how resource competition generates diversifying selection that results in adaptive divergence. We quantify an association between phenotypic and ecological divergence between two similar small fishes, brook (Culaea inconstans) and ninespine (Pungitius pungitius) sticklebacks, in replicate northern Ontario lakes, Canada. The two species partition resources and habitat, where they coexist, and brooks that coexist with ninespines are more benthically specialized in body form and diet than brooks from local allopatric populations. Here we test various explanations for this pattern. Chance is unlikely to have been the primary cause because divergence is replicated in three separate populations. Preliminary comparisons indicate that resource availability and a variety of abiotic ecological conditions are generally similar between sympatric and allopatric sites, and so do not readily account for the divergence. Biased colonization or extinction is less likely to account for the divergence because character values in sympatry tend to exceed those in allopatry, as expected if they have repeatedly evolved under diversifying selection. Recent studies have also demonstrated that these two species compete, and that competitive effects are more severe for allopatric compared to sympatric brook forms, as predicted if divergence reflects the ghost of competition past. Ongoing studies indicate heritable variation in this system. Our results suggest that even small amounts of character shifts can influence competition and hence relative fitness, further implicating a role for ECD in the evolution of biodiversity.Electronic Supplementary Material Supplementary material is available for this article at     

Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury

Ventilator-induced lung injury (VILI) is an inflammatory process that can be attenuated by lung protective ventilation strategies. Our objectives to further investigate the pathogenesis of ALI and VILI and the mechanism of lung protection in these syndromes were: 1) to determine if plasma measurements of soluble TNF receptor I (sTNFRI) and II (sTNFRII) would predict the development of ALI and mortality in a small single center trial; 2) to test the predictive value of these markers and of TNF-alpha in a larger, broader group of patients with ALI; 3) to test the hypothesis that low tidal volume ventilation (LTVV) would be associated with a decrease in plasma levels of TNF-alpha, sTNFRI, and sTNFRII. In the single center study, sTNFRI and II levels were higher in patients at risk for and with ALI, but they did not predict the development of the syndrome. In the multicenter trial sTNFRI and II were strongly associated with mortality (OR 5.76/1 log10 increment in receptor level; 95% CI 2.63-12.6 and OR 2.58; 95% CI 1.05-6.31, respectively) and morbidity measured as fewer nonpulmonary organ failure-free and ventilator-free days. The LTVV strategy was associated with an attenuation of plasma sTNFRI levels. In vitro, stimulated A549 cells release sTNFRI but not sTNRFII. In conclusion, plasma levels of sTNFRI and II can serve as biomarkers for morbidity and mortality in patients with ALI. Furthermore, LTVV is associated with a specific decrease in sTNFRI levels. This suggests that one beneficial effect of LTVV may be to attenuate alveolar epithelial injury.     

Synthetic genetic array analysis of the PtdIns 4-kinase Pik1p identifies components in a Golgi-specific Ypt31/rab-GTPase signaling pathway

Phosphorylated derivatives of phosphatidylinositol are essential regulators of both endocytic and exocytic trafficking in eukaryotic cells. In Saccharomyces cerevisiae, the phosphatidylinositol 4-kinase, Pik1p generates a distinct pool of PtdIns(4)P that is required for normal Golgi structure and secretory function. Here, we utilize a synthetic genetic array analysis of a conditional pik1 mutant to identify candidate components of the Pik1p/PtdIns(4)P signaling pathway at the Golgi. Our data suggest a mechanistic involvement for Pik1p with a specific subset of Golgi-associated proteins, including the Ypt31p rab-GTPase and the TRAPPII protein complex, to regulate protein trafficking through the secretory pathway. We further demonstrate that TRAPPII specifically functions in a Ypt31p-dependent pathway and identify Gyp2p as the first biologically relevant GTPase activating protein for Ypt31p. We propose that multiple stage-specific signals, which may include Pik1p/PtdIns(4)P, TRAPPII and Gyp2p, impinge upon Ypt31 signaling to regulate Golgi secretory function.     

Post-translational processing of beta-secretase in Alzheimer's disease

Beta-amyloid is released into the brains of Alzheimer's patients, where it aggregates and causes damage to neurons. It is cleaved proteolytically from a large transmembrane glycoprotein amyloid precursor protein by a membrane-bound protease, known as beta-secretase identified previously as the acid protease, Asp-2. We have shown previously that beta-secretase is up-regulated by increased intracellular cholesterol, and down-regulated by cholesterol biosynthesis inhibition. Here we show using mass spectrometry that discrete changes in the glycosylation and palmitoylation of beta-secretase occur when cells expressing it are treated with statins.